This project is designed to evaluate the mechanisms involved in the response of the distal tubule to changes in chloride reabsorption. These studies are based upon the observations from animal studies that suggest that the pattern of anion delivery and the reabsorbability of the distal tubule are critical determinants of the animal's response to various acid-base parameters. These studies will focus upon the effect of the pattern of distal tubular chloride delivery upon distal tubule reabsorption during metabolic acidosis. Hyperchloremia will then be induced by chronic respiratory alkalosis. The situation of hypochloremia will be studied by inducing respiratory acidosis and phera perhaps hypotonic volume expansion. The results of these studies will then be compared to those situations in which distal chloride delivery is increased while plasma chloride concentration is not changed (e.g. during mannitol loading).